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Although previous studies have reported correlations between alpha oscillations and the "retention" subprocess of working memory (WM), causal evidence has been limited in human neuroscience due to the lack of delicate modulation of human brain oscillations. Conventional transcranial alternating current stimulation (tACS) is not suitable for demonstrating the causal evidence for parietal alpha oscillations in WM retention because of its inability to modulate brain oscillations within a short period (i.e., the retention subprocess). Here, we developed an online phase-corrected tACS system capable of precisely correcting for the phase differences between tACS and concurrent endogenous oscillations. This system permits the modulation of brain oscillations at the target stimulation frequency within a short stimulation period and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to participants during the retention subprocess of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. These findings strongly support a causal link between alpha oscillations and WM retention and illustrate the broad application prospects of phase-corrected tACS.
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Memória de Curto Prazo , Estimulação Transcraniana por Corrente Contínua , Humanos , Memória de Curto Prazo/fisiologia , Encéfalo/fisiologia , CogniçãoRESUMO
Neural oscillations are critical to understanding the synchronisation of neural activities and their relevance to neurological disorders. For instance, the amplitude of beta oscillations in the subthalamic nucleus has gained extensive attention, as it has been found to correlate with medication status and the therapeutic effects of continuous deep brain stimulation in people with Parkinson's disease. However, the frequency stability of subthalamic nucleus beta oscillations, which has been suggested to be associated with dopaminergic information in brain states, has not been well explored. Moreover, the administration of medicine can have inverse effects on changes in frequency and amplitude. In this study, we proposed a method based on the stationary wavelet transform to quantify the amplitude and frequency stability of subthalamic nucleus beta oscillations and evaluated the method using simulation and real data for Parkinson's disease patients. The results suggest that the amplitude and frequency stability quantification has enhanced sensitivity in distinguishing pathological conditions in Parkinson's disease patients. Our quantification shows the benefit of combining frequency stability information with amplitude and provides a new potential feedback signal for adaptive deep brain stimulation.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/terapia , Doença de Parkinson/fisiopatologia , Humanos , Estimulação Encefálica Profunda/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Ritmo beta/fisiologia , Ritmo beta/efeitos dos fármacos , Antiparkinsonianos/uso terapêutico , Análise de OndaletasRESUMO
BACKGROUND: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) and subthalamic nucleus (STN) is employed for the treatment of dystonia. Pallidal low-frequency oscillations have been proposed as a pathophysiological marker for dystonia. However, the role of subthalamic oscillations and STN-GPi coupling in relation to dystonia remains unclear. OBJECTIVE: We aimed to explore oscillatory activities within the STN-GPi circuit and their correlation with the severity of dystonia and efficacy achieved by DBS treatment. METHODS: Local field potentials were recorded simultaneously from the STN and GPi from 13 dystonia patients. Spectral power analysis was conducted for selected frequency bands from both nuclei, while power correlation and the weighted phase lag index were used to evaluate power and phase couplings between these two nuclei, respectively. These features were incorporated into generalized linear models to assess their associations with dystonia severity and DBS efficacy. RESULTS: The results revealed that pallidal theta power, subthalamic beta power and subthalamic-pallidal theta phase coupling and beta power coupling all correlated with clinical severity. The model incorporating all selected features predicts empirical clinical scores and DBS-induced improvements, whereas the model relying solely on pallidal theta power failed to demonstrate significant correlations. CONCLUSIONS: Beyond pallidal theta power, subthalamic beta power, STN-GPi couplings in theta and beta bands, play a crucial role in understanding the pathophysiological mechanism of dystonia and developing optimal strategies for DBS.
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Estimulação Encefálica Profunda , Distonia , Globo Pálido , Núcleo Subtalâmico , Humanos , Estimulação Encefálica Profunda/métodos , Globo Pálido/fisiopatologia , Globo Pálido/fisiologia , Núcleo Subtalâmico/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Distonia/terapia , Distonia/fisiopatologia , Índice de Gravidade de Doença , Idoso , Adulto Jovem , Resultado do TratamentoRESUMO
PURPOSE: To explore the impact of different intraoperative intraocular pressure (IOP) settings on the safety and prognosis in phacoemulsification. METHODS: Age related cataract patients who met the inclusion criteria and underwent phacoemulsification by using active sentry handpiece and active fluidics system. According to different intraoperative IOP settings during surgery, they were randomly divided into two groups: the 20mmHg group and the 60mmHg group. The best corrected visual acuity (BCVA), cumulative dissipated energy (CDE), total U/S time, active surge mitigation (ASM), estimated fluid usage (EFU) as well as the changes in corneal thickness (CT), corneal epithelial layer thickness (CELT) and endothelial cell density (ECD) were collected. The post-operative follow-up was only 1 day. RESULTS: A total of 110 cases (110 eyes) were included in the study. There were 55 eyes in each group. There was no statistically significant difference in postoperative BCVA (p = 0.839). The CDE, total U/S time and EFU during surgery were (5.22 ± 3.31), (30.60 ± 15.06), (45.07 ± 12.68) and (4.70 ± 2.83), (27.39 ± 13.75), (42.38 ± 11.93) in the 20mmHg group and 60mmHg group (p = 0.381, 0.246, 0.254). The ASM during surgery in the 20mmHg group and 60mmHg group were (0.95 ± 2.77) and (7.24 ± 6.34), respectively. The 20mmHg group showed a significant decrease in ASM (p < 0.001). There was no statistically significant difference in the changes in CT, CELT and ECD before and after surgery between the two groups (p = 0.913, 0.825, 0.624). Both groups did not experience any intraoperative complications, such as posterior capsule rupture. CONCLUSION: A lower IOP setting of 20 mmHg can significantly reduce the occurrence of intraoperative surges during phacoemulsification. And there was no increase in rate of complications. TRIAL REGISTRATION: The trial registration number is ChiCTR2100050240. The registered date is August 24th, 2021.
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Pressão Intraocular , Facoemulsificação , Acuidade Visual , Humanos , Facoemulsificação/métodos , Masculino , Feminino , Pressão Intraocular/fisiologia , Idoso , Acuidade Visual/fisiologia , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Idoso de 80 Anos ou mais , Seguimentos , Catarata/complicações , Catarata/fisiopatologia , Endotélio Corneano/patologiaRESUMO
BACKGROUND AND OBJECTIVE: The balance between neural oscillations provides valuable insights into the organisation of neural oscillations related to brain states, which may play important roles in dystonia. We aim to investigate the relationship of the balance in the globus pallidus internus (GPi) with the dystonic severity under different muscular contraction conditions. METHODS: Twenty-one patients with dystonia were recruited. All of them underwent bilateral GPi implantation, and local field potentials (LFPs) from the GPi were recorded via simultaneous surface electromyography. The power spectral ratio between neural oscillations was computed as the measure of neural balance. This ratio was calculated under high and low dystonic muscular contraction conditions, and its correlation with the dystonic severity was assessed using clinical scores. RESULTS: The power spectral of the pallidal LFPs peaked in the theta and alpha bands. Within participant comparison showed that the power spectral of the theta oscillations significantly increased during high muscle contraction compared with that during low contraction. The power spectral ratios between the theta and alpha, theta and low beta, and theta and high gamma oscillations were significantly higher during high contraction than during low contraction. The total score and motor score were associated with the power spectral ratio between the low and high beta oscillations, which was correlated with the dystonic severity both during high and low contractions. The power spectral ratios between the low beta and low gamma and between the low beta and high gamma oscillations showed a significantly positive correlation with the total score during both high and low contractions; a correlation with the motor scale score was found only during high contraction. Meanwhile, the power spectral ratio between the theta and alpha oscillations during low contraction showed a significantly negative correlation with the total score. The power spectral ratios between the alpha and high beta, alpha and low gamma, and alpha and high gamma oscillations were significantly correlated with the dystonic severity only during low contraction. CONCLUSION: The balance between neural oscillations, as quantified by the power ratio between specific frequency bands, differed between the high and low muscular contraction conditions and was correlated with the dystonic severity. The balance between the low and high beta oscillations was correlated with the dystonic severity during both conditions, making this parameter a new possible biomarker for closed-loop deep brain stimulation in patients with dystonia.
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Estimulação Encefálica Profunda , Distonia , Distúrbios Distônicos , Humanos , Globo Pálido , Distonia/terapia , Distúrbios Distônicos/terapia , EletromiografiaRESUMO
Methylated CpG binding protein 2 (MeCP2) plays an important role in the development and normal function of the neural system. Abnormally high expression of MECP2 leads to a subtype of autism called MECP2 duplication syndrome and MECP2 is considered one of the key pathogenic genes for autism spectrum disorders. However, the effect of MECP2 overexpression on neural activity is still not fully understood. Thus, transgenic (TG) animals that abnormally overexpress MeCP2 are important disease models in research on neurological function and autism. To create an animal model with a stronger and more stable autism phenotype, this study established a human MECP2 TG rat model and evaluated its movement ability, anxiety, and social behavior through behavioral tests. The results showed that MECP2 TG rats had an abnormally increased anxiety phenotype and social deficits in terms of abnormal social approach and social novelty preference, but no movement disorder. These autism-like behavioral phenotypes suggest that human MECP2 TG rats are suitable models for studying autism as they show more severe social deficit phenotypes and without interference from movement disorders affecting other phenotypes, which is an issue for mouse models with MECP2 duplication. In addition, this study performed preliminary exploration of the influence of the human MECP2 transgene on neural oscillation stability of the medial prefrontal cortex (mPFC), which is an important brain region for social interactions. Oscillation stability in MECP2 TG rats showed abnormal responses to social conditions. Overall, the results of this study provide a new research tool for understanding the mechanism of social impairment and treatment of autism. The results also provide evidence for the influence of MECP2 duplication on mPFC neural activity.
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Transtorno Autístico , Deficiência Intelectual Ligada ao Cromossomo X , Proteína 2 de Ligação a Metil-CpG , Animais , Humanos , Camundongos , Ratos , Ansiedade/genética , Transtorno Autístico/genética , Encéfalo/metabolismo , Modelos Animais de Doenças , Deficiência Intelectual Ligada ao Cromossomo X/genética , Proteína 2 de Ligação a Metil-CpG/genética , Proteína 2 de Ligação a Metil-CpG/metabolismo , Camundongos Transgênicos , Ratos TransgênicosRESUMO
Autophagy has been implicated in stroke. Our previous study showed that the FoxO3 transcription factor promotes autophagy after transient cerebral ischemia/reperfusion (I/R). However, whether the Akt/FoxO3 signaling pathway plays a regulatory role in autophagy in cerebral I/R-induced oxidative stress injury is still unclear. The present study aims to investigate the effects of the Akt/FoxO3 signaling pathway on autophagy activation and neuronal injury in vitro and in vivo. By employing LY294002 or insulin to regulate the Akt/FoxO3 signaling pathway, we found that insulin pretreatment increased cell viability, decreased reactive oxygen species production, and enhanced the expression of antiapoptotic and autophagy-related proteins following H2O2 injury in HT22 cells. In addition, insulin significantly decreased neurological deficit scores and infarct volume and increased the expression of antiapoptotic and autophagy-related proteins following I/R injury in rats. However, LY294002 showed the opposite effects under these conditions. Altogether, these results indicate that Akt/FoxO3 signaling pathway activation inhibited oxidative stress-mediated cell death through activation of autophagy. Our study supports a critical role for the Akt/FoxO3 signaling pathway in autophagy activation in stroke.
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Isquemia Encefálica , Insulinas , AVC Isquêmico , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Peróxido de Hidrogênio/farmacologia , Transdução de Sinais , Estresse Oxidativo , Autofagia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/farmacologia , Insulinas/metabolismo , Insulinas/farmacologia , Encéfalo/metabolismo , ApoptoseRESUMO
OBJECTIVE: Our previous study found that ErbB4 gene expression was changed after oxygen-glucose deprivation/reperfusion (OGD/R). However, the exact role and mechanism of ErbB4 in brain ischemia are largely unknown. In this study, we explored the protective effects of ErbB4 and its possible mechanism after OGD/R. METHODS: Cerebral ischemia/reperfusion (I/R) injury model was established in vitro and in vivo. Cell viability, apoptosis, and ROS production were measured by MTT, TUNEL, and fluorescent probe 2', 7'-dichlorofluorescein diacetate (DCFH-DA). Infarct size was evaluated by TTC. We performed bioinformatics analyses to screen for novel key genes involved in ErbB4 changes. RNA-Seq was used to transcriptome analysis. RNA and protein expression were detected by quantitative RTâPCR and western bloting. RESULTS: The expression of 80-kDa ErbB4 decreased after cerebral I/R injury in vitro and in vivo. Co-expression network analysis revealed that ErbB4 expression was correlated with the changes in Adrb1, Adrb2, Ldlr, and Dab2. Quantitative RTâPCR revealed that the mRNA expression levels of Adrb1, Adrb2, and Dab2 were upregulated, and that of Ldlr was decreased after OGD/R. Activation of ErbB4 expression by neuregulin 1 (NRG1) significantly promoted cell survival, attenuated hippocampal apoptosis, and decreased ROS production after OGD/R. Furthermore, the elimination of ErbB4 using a specific siRNA reversed these beneficial effects. CONCLUSION: Our data revealed the neuroprotective effects of ErbB4 against OGD/R injury, and the action could be related to changes in the ErbB4 membrane-associated fragment and the expression of Adrb1, Adrb2, Ldlr, and Dab2.
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PURPOSE: We develop a new risk score to predict patients with stroke-associated pneumonia (SAP) who have an acute intracranial hemorrhage (ICH). METHOD: We applied logistic regression to develop a new risk score called ICH-LR2S2. It was derived from examining a dataset of 70,540 ICH patients between 2015 and 2018 from the Chinese Stroke Center Alliance (CSCA). During the training of ICH-LR2S2, patients were randomly divided into two groups - 80% for the training set and 20% for model validation. A prospective test set was developed using 12,523 patients recruited in 2019. To further verify its effectiveness, we tested ICH-LR2S2 on an external dataset of 24,860 patients from the China National Stroke Registration Management System II (CNSR II). The performance of ICH-LR2S2 was measured by the area under the receiver operating characteristic curve (AUROC). RESULTS: The incidence of SAP in the dataset was 25.52%. A 24-point ICH-LR2S2 was developed from independent predictors, including age, modified Rankin Scale, fasting blood glucose, National Institutes of Health Stroke Scale admission score, Glasgow Coma Scale score, C-reactive protein, dysphagia, Chronic Obstructive Pulmonary Disease, and current smoking. The results showed that ICH-LR2S2 achieved an AUC = 0.749 [95% CI 0.739-0.759], which outperforms the best baseline ICH-APS (AUC = 0.704) [95% CI 0.694-0.714]. Compared with the previous ICH risk scores, ICH-LR2S2 incorporates fasting blood glucose and C-reactive protein, improving its discriminative ability. Machine learning methods such as XGboost (AUC = 0.772) [95% CI 0.762-0.782] can further improve our prediction performance. It also performed well when further validated by the external independent cohort of patients (n = 24,860), ICH-LR2S2 AUC = 0.784 [95% CI 0.774-0.794]. CONCLUSION: ICH-LR2S2 accurately distinguishes SAP patients based on easily available clinical features. It can help identify high-risk patients in the early stages of diseases.
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Pneumonia , Acidente Vascular Cerebral , Glicemia , Proteína C-Reativa , Hemorragia Cerebral/complicações , Humanos , Hemorragias Intracranianas/complicações , Pneumonia/complicações , Prognóstico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment. The efficacies of tDCS combination therapies have not been investigated deliberately. This review aims to evaluate the clinical efficacy of tDCS as a monotherapy and in combination with medication, psychotherapy, and ECT for treating adult patients with major depressive disorder (MDD) and identified the factors influencing treatment outcome measures (i.e. depression score, dropout, response, and remission rates). METHODS: The systematic review was performed in PubMed/Medline, EMBASE, PsycINFO, Web of Sciences, and OpenGrey. Two authors performed independent literature screening and data extraction. The primary outcomes were the standardized mean difference (SMD) for continuous depression scores after treatment and odds ratio (OR) dropout rate; secondary outcomes included ORs for response and remission rates. Random effects models with 95% confidence intervals were employed in all outcomes. The overall effect of tDCS was investigated by meta-analysis. Sources of heterogeneity were explored via subgroup analyses, meta-regression, sensitivity analyses, and assessment of publication bias. RESULTS: Twelve randomised, sham-controlled trials (active group: N = 251, sham group: N = 204) were included. Overall, the integrated depression score of the active group after treatment was significantly lower than that of the sham group (g = - 0.442, p = 0.017), and further analysis showed that only tDCS + medication achieved a significant lower score (g = - 0.855, p < 0.001). Moreover, this combination achieved a significantly higher response rate than sham intervention (OR = 2.7, p = 0.006), while the response rate remained unchanged for the other three therapies. Dropout and remission rates were similar in the active and sham groups for each therapy and also for the overall intervention. The meta-regression results showed that current intensity is the only predictor for the response rate. None of publication bias was identified. CONCLUSION: The effect size of tDCS treatment was obviously larger in depression score compared with sham stimulation. The tDCS combined selective serotonin re-uptake inhibitors is the optimized therapy that is effective on depression score and response rate. tDCS monotherapy and combined psychotherapy have no significant effects. The most important parameter for optimization in future trials is treatment strategy.
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Transtorno Depressivo Maior , Estimulação Transcraniana por Corrente Contínua , Adulto , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Psicoterapia , Resultado do TratamentoRESUMO
Autophagy has been implicated in neurodegenerative diseases. Forkhead box O3 (FoxO3) transcription factors promote autophagy in heart and inhibit oxidative damage. Here we investigate the role of FoxO3 transcription factors in regulating autophagy after oxidative stress injury in immortalized mouse hippocampal cell line (HT22). The present study confirms that hydrogen peroxide (H2O2) injury could induce autophagy and FoxO3 activation in HT22 cells. In addition, overexpression of FoxO3 enhanced H2O2-induced autophagy activation and suppressed neuronal cell damage, while knockdown of FoxO3 reduced H2O2-induced autophagy activation and exacerbated neuronal cell injury. Inhibition of autophagy by 3-methyladenine (3-MA) resulted in reduced cell viability, increased production of reactive oxygen species (ROS), promoted nuclear condensation, and decreased expression of antiapoptotic and autophagy-related proteins, indicating that autophagy may have protective effects on H2O2-induced injury in HT22 cells. Moreover, overexpression of FoxO3 prevented exacerbation of brain damage induced by 3-MA. Taken together, these results show that activation of FoxO3 could induce autophagy and inhibit H2O2-induced damage in HT22 cells. Our study demonstrates the critical role of FoxO3 in regulating autophagy in brain.
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Peróxido de Hidrogênio , Animais , Apoptose/efeitos dos fármacos , Autofagia , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Estresse Oxidativo , Espécies Reativas de OxigênioRESUMO
Understanding the functional dynamics of neural oscillations in the sensory thalamus is essential for elucidating the perception and modulation of neuropathic pain. Local field potentials were recorded from the sensory thalamus of twelve neuropathic pain patients. Single and combinational neural states were defined by the activity state of a single or paired oscillations. Relationships between the duration or occurrence rate of neural state and pre-operative pain level or pain relief induced by deep brain stimulation were evaluated. Results showed that the occurrence rate of the single neural state of low-beta oscillation was significantly correlated with pain relief. The duration and occurrence rate of combinational neural states of the paired low-beta with delta, theta, alpha, high-beta or low-gamma oscillations were more significantly correlated with pain relief than the single neural states. Moreover, these significant combinational neural states formed a local oscillatory network with low-beta oscillation as a key node. The results also showed correlations between measures of combinational neural states and subjective pain level as well. The duration of combinational neural states of paired alpha with delta or theta oscillations and the occurrence rate of neural states of the paired delta with low-beta or low-gamma oscillations were significantly correlated with pre-operative pain level. In conclusion, this study revealed that the integration of oscillations and the functional dynamics of neural states were differentially involved in modulation and perception of neuropathic pain. The functional dynamics could be biomarkers for developing neural state-dependent deep brain stimulation for neuropathic pain.
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Neuralgia , Tálamo , Humanos , Neuralgia/terapiaRESUMO
BACKGROUND: Subcortical structures, including the basal ganglia, have been proposed to be crucial for arousal, consciousness, and behavioural responsiveness. How the basal ganglia contribute to the loss and recovery of consciousness during anaesthesia has, however, not yet been well characterised. METHODS: Twelve patients with advanced Parkinson's disease, who were undergoing deep brain stimulation (DBS) electrode implantation in the subthalamic nucleus (STN), were included in this study. Local field potentials (LFPs) were recorded from the DBS electrodes and EEG was recorded from the scalp during induction of general anaesthesia (with propofol and sufentanil) and during tracheal intubation. Neural signatures of loss of consciousness and of the expected arousal during intubation were sought in the STN and EEG recordings. RESULTS: Propofol-sufentanil anaesthesia resulted in power increases in delta, theta, and alpha frequencies, and broadband power decreases in higher frequencies in both STN and frontal cortical areas. This was accompanied by increased STN-frontal cortical coherence only in the alpha frequency band (119 [68]%; P=0.0049). We observed temporal activity changes in STN after tracheal intubation, including power increases in high-beta (22-40 Hz) frequency (98 [123]%; P=0.0064) and changes in the power-law exponent in the power spectra at lower frequencies (2-80 Hz), which were not observed in the frontal cortex. During anaesthesia, the dynamic changes in the high-gamma power in STN LFPs correlated with the power-law exponent in the power spectra at lower frequencies (2-80 Hz). CONCLUSIONS: Apart from similar activity changes in both STN and cortex associated with anaesthesia-induced unresponsiveness, we observed specific neuronal activity changes in the STN in response to the anaesthesia and tracheal intubation. We also show that the power-law exponent in the power spectra in the STN was modulated by tracheal intubation in anaesthesia. Our results support the hypothesis that subcortical nuclei may play an important role in the loss and return of responsiveness.
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Anestésicos Intravenosos/farmacologia , Estimulação Encefálica Profunda/métodos , Eletroencefalografia/métodos , Intubação Intratraqueal/métodos , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Anestesia Geral/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propofol/farmacologia , Sufentanil/farmacologiaRESUMO
BACKGROUND: The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) in Parkinson's disease (PD) and is believed to serve a role in sensorimotor integration. In addition to therapeutic neuromodulation, DBS facilitates the recording of local-field potentials (LFPs) in order to further understand the neurophysiological basis of disease. The capacity to wirelessly transmit these signals in real time has overcome the obstacle of externalization of electrodes during LFP recordings. OBJECTIVE: Using the G102RS device (PINS Medical, China), we investigated the LFP changes in response to mechanical pain stimulation to further elucidate the representation of pain sensation in the basal ganglia. METHODS: LFPs from 2 patients who had undergone bilateral STN-DBS were wirelessly recorded during no stimulation, low-frequency stimulation (60 and 90 Hz), and high-frequency stimulation (130 and 150 Hz) while introducing painful and nonpainful stimuli. Power spectral analysis was conducted to compare the changes in ß frequency (13-30 Hz) during each stimulus. RESULTS: During painful stimuli, STN power spectra (n = 4) revealed a significant increase in ß activity compared to non-painful and no-stimulus epochs. Both low- and high-frequency stimulation produced a significant decrease in pain-related ß activity. CONCLUSION: These 2 cases have demonstrated the potential for acute noxious stimuli to exacerbate pathologic ß oscillatory activity in the STN. Our findings represent novel evidence of the neurophysiologic representation of pain in the STN of PD patients.
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Ritmo beta/fisiologia , Estimulação Encefálica Profunda/métodos , Medição da Dor/métodos , Dor/fisiopatologia , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapiaRESUMO
The quantitative characterization of movement disorders and their related neurophysiological signals is important for the management of Parkinson's disease (PD). The aim of this study is to develop a novel wearable system enabling the simultaneous measurement of both motion and other neurophysiological signals in PD patients. We designed a wearable system that consists of five motion sensors and three electrophysiology sensors to measure the motion signals of the body, electroencephalogram, electrocardiogram, and electromyography, respectively. The data captured by the sensors are transferred wirelessly in real time, and the outcomes are analyzed and uploaded to the cloud-based server automatically. We completed pilot studies to (1) test its validity by comparing outcomes to the commercialized systems, and (2) evaluate the deep brain stimulation (DBS) treatment effects in seven PD patients. Our results showed: (1) the motion and neurophysiological signals measured by this wearable system were strongly correlated with those measured by the commercialized systems (r > 0.94, p < 0.001); and (2) by completing the clinical supination and pronation frequency test, the frequency of motion as measured by this system increased when DBS was turned on. The results demonstrated that this multi-sensor wearable system can be utilized to quantitatively characterize and monitor motion and neurophysiological PD.
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Monitorização Fisiológica/instrumentação , Doença de Parkinson , Dispositivos Eletrônicos Vestíveis , Estimulação Encefálica Profunda , Eletrocardiografia , Eletroencefalografia , Eletromiografia , Humanos , Movimento , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Projetos PilotoRESUMO
PURPOSE: Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance. METHODS: To determine whether pedunculopontine nucleus stimulation improves cardiovascular responses to autonomic challenges of postural tilt and Valsalva manoeuver, eight patients with pedunculopontine nucleus deep brain stimulation were recruited to the study; two were excluded for technical reasons during testing. Participants underwent head up tilt and Valsalva manoeuver with stimulation turned ON and OFF. Continuous blood pressure and ECG waveforms were recorded during these tests. In a single patient, local field potential activity was recorded from the implanted electrode during tilt. RESULTS: The fall in systolic blood pressure after tilt was significantly smaller with stimulation ON (mean - 8.3% versus - 17.2%, p = 0.044). Valsalva ratio increased with stimulation from median 1.15 OFF to 1.20 ON (p = 0.028). Baroreflex sensitivity increased during Valsalva compared to rest with stimulation ON versus OFF (p = 0.028). The increase in baroreflex sensitivity correlated significantly with the mean depth of PPN stimulating electrode contacts. This accounted for 89% of its variance (r = 0.943, p = 0.005). CONCLUSION: PPN stimulation can modulate the cardiovascular system in patients with PD. In this study, it reduced the postural fall in systolic blood pressure during head-up tilt and improved the cardiovascular response during Valsalva, presumably by altering the neural control of baroreflex activation.
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Estimulação Encefálica Profunda/métodos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Núcleo Tegmental Pedunculopontino/fisiologia , Disautonomias Primárias/etiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Teste da Mesa Inclinada , Manobra de ValsalvaRESUMO
Aim: Autophagy was activated after cerebral ischemia reperfusion (I/R) injury. However, the molecular mechanisms underlying regulation of autophagy in cerebral I/R injury were not completely understood. Studies reported that Forked-box class O (FoxO) transcription factors involved in autophagy and might be the regulator of autophagy in multiple cells. In this study, we investigated the effects of FoxO3 on regulating autophagy after cerebral I/R injury. Materials and methods: Rats were subjected to MCAO for 2 h and reperfusion for different times, western blot was used to examine the expression of p-FoxO3, FoxO3 and the autophagic marker LC3 and Beclin-1 in penumbral region. Then rats were injected with WT-FoxO3 or TM-FoxO3 adenovirus by lateral cerebral ventricle to increase the function of FoxO3, western blot was used to examine the expression of LC3 and Beclin-1 in penumbral region. TTC and HE staining were used to evaluate the effects of increased FoxO3 activation on I/R induced brain damage. Results: Our studies showed that I/R injury resulted in induction of autophagy in penumbral brain tissue with concomitant dephosphorylation of FoxO3, consistent with increased activity of nuclear FoxO3 transcription factor. Increased FoxO3 activation led to autophagy significantly increased and had a protective effects on I/R injury. Conclusion: These data revealed an important role of FoxO3 in regulating autophagy in brain, and provided a new approach for further prevention and treatment of cerebral ischemia.
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Autofagia , Isquemia Encefálica/metabolismo , Proteína Forkhead Box O3/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. APPROACH: Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. MAIN RESULTS: This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. SIGNIFICANCE: The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations.
Assuntos
Ondas Encefálicas , Estimulação Encefálica Profunda , Neuralgia/diagnóstico , Neuralgia/fisiopatologia , Tálamo/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/prevenção & controle , Medição da Dor , Substância Cinzenta Periaquedutal/fisiopatologia , Substância Cinzenta Periaquedutal/cirurgia , Análise de Componente Principal , Análise de Regressão , Índice de Gravidade de Doença , Tálamo/cirurgiaRESUMO
Motor dysfunction is the main clinical symptom and diagnosis basis of patients with Parkinson's disease (PD). A total of 30 subjects were recruited in this study, including 15 PD patients (PD group) and 15 healthy subjects (control group). Then 5 wearable inertial sensor nodes were worn on the bilateral upper limbs, lower limbs and waist of subjects. When completing the 6 paradigm tasks, the acceleration and angular velocity signals from different parts of the body were acquired and analyzed to obtain 20 quantitative parameters which contain information about the amplitude, frequency, and fatigue degree of movements to assess the motor function. The clinical data of the two groups were statistically analyzed and compared, and then Back Propagation (BP) Neural Network was used to classify the two groups and predict the clinical score. The final results showed that most of the parameters had significant difference between the two groups, ten times of 5-fold cross validation showed that the classification accuracy of the BP Neural Network for the two groups was 90%, and the predictive accuracy of Hoehn-Yahr (H-Y) staging and unified PD rating scale (UPDRS) â ¢ score of the patients were 72.80% and 68.64%, respectively. This study shows the feasibility of quantitative assessment of motor function in PD patients using wearable sensors, and the quantitative parameters obtained in this paper may have reference value for future related research.
RESUMO
OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been successfully used to treat both Parkinson's disease (PD) and dystonia. Local field potentials (LFPs) recorded from the STN of PD patients demonstrate prominent beta frequency band activity. It is unclear whether such activity occurs in the STN in dystonia, and, if not, whether dystonia has another distinctive neural population activity in the STN. METHODS: Twelve patients with PD, and eight patients with dystonia underwent DBS electrode implantation targeting the STN. Seven dystonia patients were off medication and one was on aripiprazole and clonazepam. LFPs were recorded from the DBS electrodes in PD in the on/off medication states and in dystonia. Power spectra and temporal dynamics measured by the with Lempel-Ziv complexity of the LFPs were compared among these states. RESULTS: Normalised power spectra and Lempel-Ziv complexity of subthalamic LFPs differed between dystonia off and PD on/off, and between PD off and on over the low frequency, beta and high gamma bands. Patients with dystonia and off medication had lower beta power but higher low frequency and high gamma power than PD. Spectral power in the low beta frequency (11-20Hz) range was attenuated in medicated PD. CONCLUSION: The results suggest that dystonia and PD are characterized by different patterns of oscillatory activities even within the same nucleus, and exaggerated beta activity may relate to hypo-dopaminergic status.